Kono Takeyuki, Ozawa Hiroyuki
Department of Otolaryngology-Head Neck Surgery, Keio University School of Medicine, Japan.
Department of Otolaryngology-Head Neck Surgery, Keio University School of Medicine, Japan.
Biochim Biophys Acta Rev Cancer. 2025 Feb;1880(1):189255. doi: 10.1016/j.bbcan.2024.189255. Epub 2024 Dec 31.
The DNA damage response (DDR) is an essential mechanism for maintaining genomic stability. Although DDR-targeted therapeutic strategies are being developed in several familial cancers, evaluation of their utility in head and neck squamous cell cancer (HNSCC) is lagging. This review briefly summarizes the mechanisms of DDR and the current knowledge on discovering DDR-related predictive biomarkers in HNSCC. This review also presents novel therapeutic strategies targeting DDR pathways for HNSCC based on the synthetic lethal concept. The combination of DDR inhibitors with cytotoxic treatments such as radiotherapy, chemotherapy, and immune checkpoint inhibitors is being evaluated, and several clinical trials are ongoing in patients with HNSCC. While DDR inhibitors are considered promising treatment options, resistance to these drugs is frequently observed, and their mechanisms are currently active research areas. A better understanding of the correlation between DDR pathways and cancer biology provides new therapeutic strategies for personalized medicine in HNSCC.
DNA损伤反应（DDR）是维持基因组稳定性的重要机制。尽管针对DDR的治疗策略正在多种家族性癌症中研发，但对其在头颈部鳞状细胞癌（HNSCC）中的效用评估仍较为滞后。本综述简要总结了DDR的机制以及目前在HNSCC中发现DDR相关预测性生物标志物的知识。本综述还基于合成致死概念提出了针对HNSCC的DDR通路的新型治疗策略。目前正在评估DDR抑制剂与放疗、化疗和免疫检查点抑制剂等细胞毒性治疗的联合应用，并且针对HNSCC患者正在进行多项临床试验。虽然DDR抑制剂被认为是有前景的治疗选择，但对这些药物的耐药性经常出现，其机制目前是活跃的研究领域。更好地理解DDR通路与癌症生物学之间的相关性为HNSCC的个性化医学提供了新的治疗策略。
